Publication Date:
2013-10-19
Description:
Histone modifications are important markers of function and chromatin state, yet the DNA sequence elements that direct them to specific genomic locations are poorly understood. Here, we identify hundreds of quantitative trait loci, genome-wide, that affect histone modification or RNA polymerase II (Pol II) occupancy in Yoruba lymphoblastoid cell lines (LCLs). In many cases, the same variant is associated with quantitative changes in multiple histone marks and Pol II, as well as in deoxyribonuclease I sensitivity and nucleosome positioning. Transcription factor binding site polymorphisms are correlated overall with differences in local histone modification, and we identify specific transcription factors whose binding leads to histone modification in LCLs. Furthermore, variants that affect chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947669/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McVicker, Graham -- van de Geijn, Bryce -- Degner, Jacob F -- Cain, Carolyn E -- Banovich, Nicholas E -- Raj, Anil -- Lewellen, Noah -- Myrthil, Marsha -- Gilad, Yoav -- Pritchard, Jonathan K -- GM007197/GM/NIGMS NIH HHS/ -- HG006123/HG/NHGRI NIH HHS/ -- HG007036/HG/NHGRI NIH HHS/ -- MH084703/MH/NIMH NIH HHS/ -- R01 HG006123/HG/NHGRI NIH HHS/ -- R01 MH084703/MH/NIMH NIH HHS/ -- T32 GM007197/GM/NIGMS NIH HHS/ -- U01 HG007036/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):747-9. doi: 10.1126/science.1242429. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136359" target="_blank"〉PubMed〈/a〉
Keywords:
Binding Sites/genetics
;
Cell Line, Tumor
;
Cells/metabolism
;
Chromatin/chemistry/genetics/metabolism
;
*Gene Expression Regulation
;
*Genetic Variation
;
Genome, Human
;
Histones/chemistry/genetics/*metabolism
;
Humans
;
Polymorphism, Genetic
;
Promoter Regions, Genetic
;
Protein Processing, Post-Translational/*genetics
;
Quantitative Trait Loci
;
RNA Polymerase II/chemistry/*metabolism
;
Transcription Factors/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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